Combination of a big-h3 antagonist and an immune checkpoint inhibitor for the treatment of solid tumor

a technology of immune checkpoint inhibitor and big-h3 antagonist, which is applied in the field of big-h3 antagonist and immune checkpoint inhibitor for the treatment of solid tumor, can solve the problems of poor prognosis, inability to completely treat all individuals afflicted with cancer, and immunization checkpoint blockage, and achieve the effect of enhancing the sensitivity of a patient suffering

Pending Publication Date: 2021-11-04
INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0007]The present invention relates to a combination of a βig-h3 antagonist and of an immune checkpoint inhibitor for simultaneous or sequential use in the treatment of a patient suffering from solid tumor, and ...

Problems solved by technology

Immune checkpoint blockade has elicited clinical responses in some patients with different advanced malignancies (ie melanoma) but has not been effective in PDAC, suggesting that other factors including mechanical tension generated in desmoplastic tumor microenvironment may limit ...

Method used

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  • Combination of a big-h3 antagonist and an immune checkpoint inhibitor for the treatment of solid tumor
  • Combination of a big-h3 antagonist and an immune checkpoint inhibitor for the treatment of solid tumor
  • Combination of a big-h3 antagonist and an immune checkpoint inhibitor for the treatment of solid tumor

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examples

[0157]The following examples describe some of the preferred modes of making and practicing the present invention. However, it should be understood that the examples are for illustrative purposes only and are not meant to limit the scope of the invention.

[0158]Material and Methods

[0159]Mice

[0160]The p48-Cre;KrasG12D (KC), pdx1-Cre;KrasG12D;Ink4alArffl / fl (KIC) and pdx1-Cre;KrasG12D;p53R172H (KPC) mice have been previously described26-28. All animal protocols were reviewed and approved in accordance with the guidelines provided by the Cancer Research Center Lyon Animal Care and Use Committee.

[0161]Collection of Tissue Samples from Mice

[0162]Normal and tumoral pancreas were washed in PBS, minced into small fragments and then incubated in collagenase solution (1 mg / ml collagenase V obtained from Roche in HBSS) at 37° C. for 20 min. The spleen and peripancreatic lymph nodes were homogenized and passed through a 70 μm cell strainer to achieve single cell suspensions. Red blood cells were ...

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Abstract

To study the mechanism of βig-h3 modulation of the anti-tumoral immune response in pancreatic cancer, Inventors took advantage of engineered mouse models of spontaneous pancreatic neoplasia and cancer to evaluate the effect of depleting βig-h3 on the modulation of anti-tumor immunity and its subsequent impact on tumour growth alone and in combination with an immune checkpoint inhibitor. This association proved to be effective in vivo in this model showing a synergic effect of the therapeutic combination. Accordingly, the present invention relates to a combination of (i) an immune checkpoint inhibitor, and (ii) a βig-h3 antagonist, for simultaneous or sequential use in the treatment of a patient suffering from solid tumor, e.g. a pancreatic cancer. The present invention also provides a βig-h3 antagonist, for use in a method for enhancing sensitivity of a patient suffering from a solid tumor to an immune checkpoint inhibitor.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a combination of (i) a βig-h3 antagonist, and (ii) an immune checkpoint inhibitor, for the simultaneous or sequential use in the treatment of a patient suffering from a solid tumor, e.g. a pancreatic cancer. The present invention also provides a βig-h3 antagonist, for use in a method for enhancing sensitivity of a patient suffering from tumor to an immune checkpoint inhibitor.BACKGROUND OF THE INVENTION[0002]Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive cancer with a median survival of less than 6 months and a 5-year survival rate of 3-5%1. PDA evolves through a series of pancreatic intraepithelial neoplasias (PanINs) that are accompanied by genetic modifications. Of these, the earliest and most ubiquitous is the oncogenic activation of Kras2. In addition to the molecular and histological alterations that define cancer cells, a hallmark of PDA is the prominent stromal reaction that surrounds the neoplastic ...

Claims

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Application Information

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IPC IPC(8): C07K16/22C07K16/28A61P35/04
CPCC07K16/22C07K16/2818A61K2039/507A61P35/04C07K16/2827C07K16/18C07K2317/73C07K2317/74A61K2039/505A61P35/00
Inventor HENNINO, ANA
Owner INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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